key: cord-0918890-6lk0pxlw
authors: Moraz, M.; Jacot, D.; Papadimitriou-Olivgeris, M.; Senn, L.; Greub, G.; Jaton, K.; Opota, O.
title: Universal admission screening strategy for COVID-19 highlighted the clinical importance of reporting SARS-CoV-2 viral loads
date: 2020-11-19
journal: New Microbes New Infect
DOI: 10.1016/j.nmni.2020.100820
sha: 6c5c6ed998273ecf344421ad911f005dbaa6547e
doc_id: 918890
cord_uid: 6lk0pxlw

Previously limited to symptomatic patients, our hospital introduced on April 25, a universal admission screening strategy for COVID-19. All patients were tested by RT-PCR. We observed decreased viral loads linked to increased screening of asymptomatic patients highlighting the fact that viral load values may guide infection control decisions.

1 polymerase chain reaction (RT-PCR) was used as a crucial diagnostic tool (1). Between the 2 beginning of March and May 17, our molecular diagnostic laboratory located in a tertiary care 3 university hospital (Lausanne, Switzerland), performed more than 34'000 SARS-CoV-2 RT-PCRs 4 using three different platforms: our high throughput automated molecular diagnostic platform 5 (MDx platform) (2), the cobas SARS-CoV-2 test and the GeneXpert Xpress SARS-CoV-2. In addition 6 to qualitative "yes or no" answer, RT-PCR can provide quantitative values based on cycle threshold 7 values (Cts). To provide a precise and reliable quantitative or semi-quantitative information, 8 laboratories must transform the Ct values into viral loads using positive controls obtained from 9 viral culture and/or from calibrated positive plasmid controls. In our laboratory, we used these 10 two types of positive controls to determine the correlation between the Ct value and the viral load 11 and this calibration was performed for all our instruments (3, 4). Reporting viral load values can be 12 used i) by the laboratory as an internal quality assessment tool, ii) by clinicians to evaluate the 13 progression of the infection (in lower respiratory tract specimens or across time) or iii) to address 14 patient contagiousness and hence to guide infection control decisions (5-9). Regarding the latter 15 application and during the first deconfinement phase after the lockdown in Switzerland, the 16 benefit of reporting the viral load value appeared of utmost importance. From April 25, a universal 17 admission or pre-intervention screening strategy including asymptomatic patients was introduced 18 in our hospital. We observed an abrupt decrease of viral load in patients screened after April 25 19 compared to patients screened during the "epidemic period" where the screening strategy 20 focused mainly on symptomatic patients (Fig. 1 ). This shift is likely explained by an increase 21 screening of asymptomatic patients with low viral load compared to symptomatic individuals 22 more likely to have high viral loads. This abrupt change was confirmed by looking only at a shorter 23 period of 2 weeks just prior to the shift to the universal screening strategy. The GeneXpert SARS-24

CoV-2 test was broadly used during this period, detecting the SARS-CoV-2-specific N2 region 25 (encoding for viral nucleoprotein N2) and the E-gene (encoding for a protein of the envelope). 26

Viral load calculation was based on the E-gene as the Cts correlated with the other two platforms 27 and could be therefore compared directly. Among the very high Cts, we obtained several results 28 positive only for N2, suggesting a very low viral load at the detection limit of the GeneXpert assay 29 (10, 11). By retesting these specimens with other RT-PCR platforms and reviewing clinical data, we 30 could demonstrate that these N2 only positive results corresponded to true detection of viral 31

RNA. When only the N2 gene was positive, the reported result was "positive result, low viral load -32 quantification impossible". 33

Since April 2020, we reported all SARS-CoV-2 RT-PCR results quantitatively. This is important since 34 it provides some information regarding the robustness of the result and about the contagiousness 35 of the patients, a subject with a viral load lower than 1000 copies/ml is likely exhibiting a 36 negligible contagiousness. However, to assess contagiousness, it is important to also consider the 37 Cycle threshold

Characteristics of and Public Health Responses to the Coronavirus 68 Disease 2019 Outbreak in China

Ten years of R&D and full automation in molecular 70 diagnosis

Viral load of SARS-CoV-2 across patients and compared